TY - JOUR
T1 - Acute transplantation of glial-restricted precursor cells into spinal cord contusion injuries
T2 - Survival, differentiation, and effects on lesion environment and axonal regeneration
AU - Hill, Caitlin E.
AU - Proschel, Christoph
AU - Noble, Mark
AU - Mayer-Proschel, Margot
AU - Gensel, John C.
AU - Beattie, Michael S.
AU - Bresnahan, Jacqueline C.
PY - 2004/12
Y1 - 2004/12
N2 - Transplantation of stem cells and immature cells has been reported to ameliorate tissue damage, induce axonal regeneration, and improve locomotion following spinal cord injury. However, unless these cells are pushed down a neuronal lineage, the majority of cells become glia, suggesting that the alterations observed may be potentially glially mediated. Transplantation of glial-restricted precursor (GRP) cells-a precursor cell population restricted to oligodendrocyte and astrocyte lineages-offers a novel way to examine the effects of glial cells on injury processes and repair. This study examines the survival and differentiation of GRP cells, and their ability to modulate the development of the lesion when transplanted immediately after a moderate contusion injury of the rat spinal cord. GRP cells isolated from a transgenic rat that ubiquitously expresses heat-stable human placental alkaline phosphatase (PLAP) were used to unambiguously detect transplanted GRP cells. Following transplantation, some GRP cells differentiated into oligodendrocytes and astrocytes, retaining their differentiation potential after injury. Transplanted GRP cells altered the lesion environment, reducing astrocytic scarring and the expression of inhibitory proteoglycans. Transplanted GRP cells did not induce long-distance regeneration from corticospinal tract (CST) and raphe-spinal axons when compared to control animals. However, GRP cell transplants did alter the morphology of CST axons toward that of growth cones, and CST fibers were found within GRP cell transplants, suggesting that GRP cells may be able to support axonal growth in vivo after injury.
AB - Transplantation of stem cells and immature cells has been reported to ameliorate tissue damage, induce axonal regeneration, and improve locomotion following spinal cord injury. However, unless these cells are pushed down a neuronal lineage, the majority of cells become glia, suggesting that the alterations observed may be potentially glially mediated. Transplantation of glial-restricted precursor (GRP) cells-a precursor cell population restricted to oligodendrocyte and astrocyte lineages-offers a novel way to examine the effects of glial cells on injury processes and repair. This study examines the survival and differentiation of GRP cells, and their ability to modulate the development of the lesion when transplanted immediately after a moderate contusion injury of the rat spinal cord. GRP cells isolated from a transgenic rat that ubiquitously expresses heat-stable human placental alkaline phosphatase (PLAP) were used to unambiguously detect transplanted GRP cells. Following transplantation, some GRP cells differentiated into oligodendrocytes and astrocytes, retaining their differentiation potential after injury. Transplanted GRP cells altered the lesion environment, reducing astrocytic scarring and the expression of inhibitory proteoglycans. Transplanted GRP cells did not induce long-distance regeneration from corticospinal tract (CST) and raphe-spinal axons when compared to control animals. However, GRP cell transplants did alter the morphology of CST axons toward that of growth cones, and CST fibers were found within GRP cell transplants, suggesting that GRP cells may be able to support axonal growth in vivo after injury.
KW - Alkaline phosphatase
KW - Contusion
KW - Corticospinal tract
KW - Glial scar
KW - Glial-restricted precursor cells
KW - Hoechst
KW - Human placental alkaline phosphatase
KW - Immature astrocytes
KW - NBT/BCIP
KW - PLAP
KW - Precursor cells
KW - Proteoglycans
KW - Spinal cord injury
KW - Transplantation
UR - http://www.scopus.com/inward/record.url?scp=8644282174&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=8644282174&partnerID=8YFLogxK
U2 - 10.1016/j.expneurol.2004.05.043
DO - 10.1016/j.expneurol.2004.05.043
M3 - Article
C2 - 15530870
AN - SCOPUS:8644282174
SN - 0014-4886
VL - 190
SP - 289
EP - 310
JO - Experimental Neurology
JF - Experimental Neurology
IS - 2
ER -